A general concern in functional electrical stimulation (FES) is the changes in the extracellular microenvironment that accompany long-term electrical stimulation that can give rise to reversible and irreversible tissue damage and to neural dysfunction. We propose to fabricate and evaluate a novel series of electrochemical biosensors for monitoring the chemical microenvironment during acute and chronic neural stimulation. These biosensors, demonstrated in Phase I employ electrochemical detection of the reaction products of analyte-specific enzymes incorporated in a hydrous iridium oxide electrode matrix. They have been fabricated directly onto elements of electrode arrays currenfly employed in neural stimulation in which IrOx is used as a depolarizing, low impedance coating. These new tools will be valuable in neural prosthesis research for determining chemical imbalances which occur. Ultimately they will provide means of feedback control of artificial neural stimulation as long-lived, permanent additions to chronically implanted FES arrays. Phase II will entail developing a wider range of improved, long-lived, interference-free amperometric and potentiometric IrOx biosensors for operation in vivo (cerebrospinal fluid, braln tissue, muscle), design of stimulation and electrochemical measuring instrumentation, and in vivo studies of local extracellular chemistry during neural and muscular stimulation in the rabbit cortex. PROPOSED COMMERCIAL APPLICATION: FES electrodes and associated electronics with biosensor feedback control for intracortical prostheses for vision, hearing, tremor and sensation; sacral root prostheses for electromicturition; and peripheral nerve prostheses for motor control and sensation. Related products include electrochemically transduced enzyme-linked immunoassay kits and direct sensors for blood constituents (glucose, bilirubin, uric acid, cholesterol, etc.).